What Is Filaggrin? Its Role in Skin Barrier Function

Filaggrin is a protein found in the skin that helps maintain its health and protective barrier, shielding the body from external elements. Understanding its role provides insights into skin integrity.

The Core Identity of Filaggrin

Filaggrin originates from a larger precursor called profilaggrin. Profilaggrin is synthesized within keratohyalin granules in the granular layer of the epidermis. This precursor, encoded by the FLG gene, contains multiple repeating units of filaggrin.

As skin cells mature and move towards the surface, profilaggrin undergoes a crucial transformation. It is dephosphorylated and then broken down by enzymes into individual filaggrin monomers as cells transition to the stratum corneum.

Its Indispensable Role in Skin Barrier Function

Filaggrin monomers directly shape skin cells. They bind to and aggregate keratin intermediate filaments, condensing them into dense bundles. This aggregation flattens and compacts skin cells, forming the tightly packed structure of the stratum corneum. This process contributes significantly to the mechanical strength of the skin barrier.

Filaggrin is also important for maintaining skin hydration. In the upper stratum corneum, filaggrin breaks down into amino acids. These breakdown products form Natural Moisturizing Factors (NMFs), attracting and retaining water within skin cells, keeping the skin supple and preventing excessive water loss.

NMFs derived from filaggrin also maintain the skin’s slightly acidic surface pH, known as the acid mantle. This acidic environment supports enzyme function in skin health and protects against microorganism growth.

When Filaggrin Falls Short

When filaggrin is deficient, the skin’s protective barrier can become compromised. Such deficiencies are often linked to genetic variations in the FLG gene. A reduced amount of functional filaggrin leads to an impaired skin barrier, making the skin more susceptible to moisture loss and external influences.

Ichthyosis vulgaris is a common condition associated with filaggrin deficiency. This genetic disorder, caused by loss-of-function mutations in the FLG gene, leads to dry, scaly skin and a rough texture. The skin’s natural ability to retain water is diminished, and its structural organization is affected.

Filaggrin deficiency is also a predisposing factor for atopic dermatitis, or eczema. A compromised skin barrier, due to insufficient filaggrin, allows irritants, allergens, and microorganisms to penetrate the skin. This increased permeability can trigger immune responses and inflammation, contributing to the characteristic dryness, itching, and redness of atopic dermatitis.

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